We recently found a lysophospholipase D enzyme in rat brain that catalyzes the removal of ethanolamine and choline moieties from the alkyl ether and plasmalogen analogs of lysophosphatidylcholine and lysophosphatidylethanolamine. The enzyme requires Mg ions for activity and does not hydrolyze the substrates containing an acyl group attached at the 2-position of the glycerol. Since we reported the enzyme in brain, we found that the liver also contains lysophospholipase D. The goal of the proposed research is to characterize lysophospholipase D and to assess its role in the metabolism of lipids in different tissues and under different conditions, including diseased states. Both the tissue distribution and the subcellular distribution of the enzyme will be determined. Lysosomes will be thoroughly examined for the presence of lysophospholipase D; activity there could explain how phosphodiesters derived from lipids are removed from the lysosomes. We hope to establish the exact specificity of lysophospholipase D by purifying the enzyme. It is well known that lysophosphoglycerides are potent lysing agents and that they must not be allowed to build up in tissues. Lysophospholipase D may prove to be critically important for the removal of the ether-containing lysophosphoglycerides from tissues. Abnormalities in this function could play an important role in diseases, especially of tissues rich in ether lipids -- cancer, nervous tissue, and the circulatory system. Lysophospholipase D levels in normal and diseased tissues will be examined to assess this possibility.